Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
Osteoarthritis Research Program, Division of Orthopedics, Schroeder Arthritis Institute, University, Health Network, Toronto, ON, Canada.
Rheumatology (Oxford). 2023 May 2;62(5):1964-1971. doi: 10.1093/rheumatology/keac545.
Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms.
Two independent cohorts from St John's, NL, Canada (n = 430), and Toronto, ON, Canada (n = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts.
One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P < 2 × 10-5), were significantly associated with sustained knee pain.
Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA.
膝关节疼痛是 OA 患者寻求医疗保健的主要原因，但在进行保守和手术疼痛干预后，约 20%的患者在全膝关节置换术 (TKA) 后仍长期疼痛。本研究旨在确定 TKA 后持续性膝关节疼痛的代谢组学特征，以阐明可能的潜在机制。
本研究纳入了来自加拿大新斯科舍省圣约翰市（n=430）和安大略省多伦多市（n=495）的两个独立队列。原发性 OA 患者在 TKA 后至少 1 年使用 WOMAC 疼痛量表（五个问题）评估持续性膝关节疼痛。报告所有五个问题都有疼痛的患者被认为患有持续性膝关节疼痛。使用 Biocrates Absolute IDQ p180 试剂盒对空腹术前血浆样本进行代谢组学分析。使用逻辑回归，调整年龄、性别和 BMI，评估每个队列中代谢物与持续性膝关节疼痛之间的关联。对来自两个队列的汇总统计数据进行基于逆方差加权的随机效应荟萃分析。
一种代谢物，磷脂酰胆碱 (PC) 二酰基 (aa) C28:1（比值比=0.66，P=0.00026），以及三种代谢物比值，PC aa C32:0 与 PC aa C28:1、PC aa C28:1 与 PC aa C32:0、十四烯基肉碱 (C14:2) 与神经鞘磷脂 C20:2（比值比分别为 1.59、0.60 和 1.59，均 P<2×10-5），与持续性膝关节疼痛显著相关。
尽管还需要进一步研究，但我们的结果提供了潜在的预测生物标志物和药物靶点，它们可以作为预后不良的标志物，并在术前进行修饰，以改善膝关节疼痛和对 TKA 的手术反应。
